Dextrorphan is the dextro isomer of levorphan, this latter being an opium substance endowed with marked analgesic activity. Differently from levorphan, dextrorphan does not have any analgesic activity, nor has it any affinity for the opium receptors (and therefore it causes neither dependence nor tolerance) (Benson W. M., Stefko P. L., Randall L. O.; J. Pharmacol. Exp. Therap. 109, 189, 1953), but is endowed with a considerable antitussis action (Goodman L. S., Gilman A.: "The Pharmacological Basis of Therapeutics", page 263, McMillan Pub. Co. Inc., New York 1975).
Many investigations have shown that this compound, either in free or in conjugated form, is the major metabolite of dextromethorphan (Axelrod J., J. Pharmacol. Exp. Ther. 117, 322, 1956; Elison C., Elliott, J., Pharmacol. Exp. Ther. 144, 265, 1964; Kamm J., Taddeo A., Van Loon E., J. Pharmacol. Exp. Ther. 158, 437, 1967; Willner, Arzneim. Forsch. 13, 20, 1963), a drug which has been marketed worldwide as a sedative for tussis. It has been demonstrated indeed (Aylward M., Maddock J., Davies D. E., Protheroe D. A., Leideman T.; Eur. J. Respir. Dis. 65, 283, 1984) that the clinical efficaciousness of dextromethorphan is best correlated not to its hematic levels (which are practically negligible in correspondence of the peak time of the therapeutical effects), but to the hematic levels of dextrorphan, so that the concentration of said metabolite in the biological fluids is commonly determined for the kinetic study of dextromethorphan (Ramachander G., Williams F. D., Emele J. F.; J. Pharm. Sci. 66, 1047, 1977). The hematic levels of dextrorphan which are observed after the oral administering of dextromethorphan remain stable over longer, than three hours. But it must be remembered that the metabolic conversion of dextromethorphan into dextrorphan does not occur always in a constant and foreseeable way. In fact, this reaction depends on sex (Ramachander G., Bapatla K. R., Emele J. F.; J. Pharm. Sci. 67, 1326, 1978), i.e., it is much faster in male sex, and, like all the metabolic reactions of the exogenous substances, it can be influenced by the state of health of the patient, by his age, etc. (Goodman L. S., Gilman A.: "The Pharmacological Basis of Therapeutics", pages 16-17, Mc Millan Int. Co., New York 1975).
Another interesting consideration is that dextrorphan has a toxicity by parenteral way even lower than dextromethorphan (Benson W. M., Stefko P. L., Randall L. O.; J. Pharmacol. Exp. Therap., 109, 189, 1953). One could thus think to directly use dextrorphan as a tussis sedative agent.
But a severe hindrance to a therapeutical use thereof is constituted by the fact that this component is not absorbed when it is administered by oral way (Schanker L. S., Shore Parkhurst P. A., Brodie B. B., Hoghen C. A. M., J. Pharmacol. Exp. Therap., 120, 528, 1957).